Analysis of the sensitivity of the measured HP 13C Lac signal to specific metabolic parameters. Simulations were performed using a three-pool model representing the 13C-labeling kinetics of Glc, Pyr, and Lac in the brain (a). The model is characterized by three metabolic fluxes: the cerebral metabolic rate of glucose (CMRGlc), the conversion between pyruvate and lactate through lactate dehydrogenase (VLDH) and the exchange between blood lactate and brain tissue lactate (Vout). (b) A typical step input function for glucose fractional enrichment reaching 70% after 14 s was used. (c) The sensitivity of the Lac 13C concentration relative to the CMRGlc was assessed by varying the CMRGlc from 0.25 micromole/g/min to 1 µmol/g/min, with a nominal Lac pool size of 4 µmol/g. (d) The sensitivity of the Lac 13C concentration relative to the Lac pool size was assessed by varying the Lac pool size from 2 µmol/g to 8 µmol/g, with a nominal CMRGlc of 4 µmol/g. In (e–g), the physical parameters influencing the measured 13C HP signal were included in the differential equations of the model (T1 decay and repetitive RF pulsing). The 13C Lac signal is shown for a varying CMRGlc with a fixed endogenous Lac concentration (f) or for varying endogenous Lac concentration with a fixed CMRGlc (g).